Cardiovascular M eds Intoxication

1. Cardiovascular Meds Intoxication Zohair Al Aseri MD,FRCPC EM & CCM

2. Cardiovascular BB & CCB Intoxication Zohair Al Aseri MD,FRCPC EM & CCM

3. Introduction • a 64-year-old man in the critical bay who took an overdose of his medications. Zohair Al Aseri MD,FRCPC EM & CCM

4. has a history of hypertension, atrial fibrillation, and depression. • lethargic but arousable • reports he took about 40 tablets of immediate-release metoprolol three hours ago in an attempt to “end it all.” Zohair Al Aseri MD,FRCPC EM & CCM

5. “Is it too late for gastric decontamination? • If he is symptomatic, which therapy will you try first, and what are your options?” Zohair Al Aseri MD,FRCPC EM & CCM

6. a 2-year-old child in the pediatric area who was found playing with grandma’s bottle of verapamil controlled release 15 minutes ago. • The grandmother thinks that at most there are three tablets missing. Zohair Al Aseri MD,FRCPC EM & CCM

7. Child looks great • “Are three tablets a big deal? • Can we just watch the child for a couple of hours? • Do we need an IV and blood work? Zohair Al Aseri MD,FRCPC EM & CCM

8. Principles of Disease Pathophysiology • inhibit endogenous catecholamines such as epinephrine at the beta-receptor. Zohair Al Aseri MD,FRCPC EM & CCM

9. Selected Characteristics of Common Beta-Blockers Zohair Al Aseri MD,FRCPC EM & CCM

10. Principles of Disease Pathophysiology • Beta-blockers are rapidly absorbed after oral ingestion, and the peak effect of normal-release preparations occurs in 1 to 4 hours.  • Hepatic metabolism on first pass results in significantly less bioavailability after oral dosing than with IV injection (1 : 40 for propranolol). • Volume of distribution for various beta-blockers generally exceeds 1 L/kg, meaning tissue concentrations exceed those of serum. Zohair Al Aseri MD,FRCPC EM & CCM

11. Principles of Disease Pathophysiology • Therefore, hemodialysis is not efficacious for most beta-blockers. • Protein binding varies from 0% for sotalol to 93% for propranolol. • Elimination half-lives vary from 8 to 9 minutes for esmolol to as long as 24 hours for nadolol and others  Zohair Al Aseri MD,FRCPC EM & CCM

12. MANIFESTATIONS AND COMPLICATIONS OF BETA-BLOCKER OVERDOSEIN ORDER OF DECREASING FREQUENCY Zohair Al Aseri MD,FRCPC EM & CCM

13. Diagnostic Strategies • Diagnosis and management depend on the clinical picture • Hypoglycemia is common in children Zohair Al Aseri MD,FRCPC EM & CCM

14. Management • IV fluids • Oxygen • Monitoring of card for rhythm and respirations. • Activated charcoal is unproven treatment. • Multiple-dose charcoal without supporting evidence for an improvement in outcome. Zohair Al Aseri MD,FRCPC EM & CCM

15. Management • Onset of toxicity is so uniformly early that absence of symptoms 4 hours after ingestion implies a low risk for subsequent morbidity unless a delayed-release preparation is involved. Zohair Al Aseri MD,FRCPC EM & CCM

16. Management Hypotension, Bradycardia, and Atrioventricular Block • Catecholamines with chronotropic and dromotropic as well as inotropic and vasopressor effects should be chosen. Zohair Al Aseri MD,FRCPC EM & CCM

17. Management • It is rare for one catecholamine to be equally effective against all four toxic effects, so combinations of drugs are often used in severe cases. Zohair Al Aseri MD,FRCPC EM & CCM

18. Management The first step in the treatment of beta-blocker overdose is • Atropine • Glucagon • Crystalloid fluids. Zohair Al Aseri MD,FRCPC EM & CCM

19. Management • A dose of atropine may quickly wear off or be ineffective, so infusion of more potent drugs or cardiac pacing is usually necessary. • Atropine (0.5 mg for adults, 0.02 mg/kg for children, minimum 0.10 mg) should be given before vagal stimuli such as tracheal or gastric intubation. Zohair Al Aseri MD,FRCPC EM & CCM

20. Management Glucagon • Does not depend on beta-receptors for its action, has both inotropic and chronotropic effects. • it helps to counteract the hypoglycemia induced by beta-blocker overdose. • is given as a 5- to 10-mg IV bolus Zohair Al Aseri MD,FRCPC EM & CCM

21. Management Glucagon • Because of its short (20-minute) half-life, an infusion of 2 to 5 mg/hr (or for children, 0.05–0.1 mg/kg bolus, then 0.05–0.1 mg/kg/hr) should be started immediately after the bolus. • With cumulative large doses, glucagon should be diluted in 5% glucose in water for constant infusion. Zohair Al Aseri MD,FRCPC EM & CCM

22. Management Glucagon • Side effects include nausea and vomiting in most patients, mild hyperglycemia, hypokalemia, and allergic reactions. • The response to glucagon alone is often inadequate. Zohair Al Aseri MD,FRCPC EM & CCM

23. Management sodium bicarbonate • Sodium channel blockade, manifested by QRS widening, occasionally occurs with beta-blocker intoxication and may respond to infusion of sodium bicarbonate. Zohair Al Aseri MD,FRCPC EM & CCM

24. Management • In hypotensive patients, 20 to 40 mL/kg of normal saline or Ringer's lactate solution can be infused and repeated. • If hypotension or bradycardia persists, other cardioactive drugs are indicated. • dopamine, or epinephrine. Zohair Al Aseri MD,FRCPC EM & CCM

25. Management • Other catecholamines include norepinephrine, dobutamine, and phenylephrine. • Often, norepinephrine or dopamine is added to beta-agonists such as isoproterenol that lack vasopressor activity. Zohair Al Aseri MD,FRCPC EM & CCM

26. Treatment Stellpflug SJ, Harris CR, Engebretsen KM, et al. Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin. ClinToxicol 2010;48: 227-229.42 High-Dose Insulin Euglycemia (HDIE) Therapy • There are no randomized controlled human trials. • There are multiple case reports of the hemodynamic improvement after institution of HDIE. Zohair Al Aseri MD,FRCPC EM & CCM

27. Management Insulin • High-dose (0.5–1 unit/kg/hr) insulin infusion for hemodynamically significant toxicity is often given before traditional pressors. • Beta-blocker toxicity shifts myocardial energy preferences from free fatty acids to carbohydrates, and insulin increases myocardial carbohydrate uptake. • Recent canine and porcine models showed the benefit of insulin infusion up to 10 units/kg/hr. Zohair Al Aseri MD,FRCPC EM & CCM

28. Management Insulin • Glucose, usually in 5 to 10% solutions, is infused to maintain a serum glucose of approximately 100 mg/dL. • The combination of glucose and high-dose insulin augments myocardial contraction independent of beta-receptors. • Glucose and potassium should be monitored frequently during infusion and supplemented as needed to maintain euglycemia and eukalemia. Zohair Al Aseri MD,FRCPC EM & CCM

29. Management • Refractory cases of bradycardia may respond to an external or transvenous pacemaker. Zohair Al Aseri MD,FRCPC EM & CCM

30. Management Calcium • Because deleterious effects on calcium transport may contribute to beta-blocker toxicity, IV calcium salts have been suggested for treating hypotension. • calcium should be given cautiously and less aggressively than for cases of calcium channel blocker overdose. • Constant infusions are safer than boluses. • Give 1 to 2 g over 5 to 10 minutes, monitoring closely for effect. Zohair Al Aseri MD,FRCPC EM & CCM

31. Management Ventricular Dysrhythmias • Although uncharacteristic, ventricular tachydysrhythmias do occur sometimes. • Cardioversion and defibrillation are indicated for ventricular tachycardia and ventricular fibrillation, respectively, following American Heart Association guidelines. • Pulsatile ventricular tachycardia or frequent ventricular ectopy can most safely be treated with lidocaine. Zohair Al Aseri MD,FRCPC EM & CCM

32. Management Extracorporeal Elimination and Circulatory Assistance • Hemodialysis or hemoperfusion may be beneficial for atenolol, nadolol, sotalol, and timolol, the beta-blockers with lower Vd, lower protein binding, and greater hydrophilicity. Zohair Al Aseri MD,FRCPC EM & CCM

33. Management Extracorporeal Elimination and Circulatory Assistance • can be lifesaving in cases of refractory hypotension.  • To be successful, such heroic measures must be taken before prolonged hypotension leads to multiorgan ischemic injury. Zohair Al Aseri MD,FRCPC EM & CCM

34. TREATMENT OF BETA-BLOCKER POISONING Zohair Al Aseri MD,FRCPC EM & CCM

35. Zohair Al Aseri MD,FRCPC EM & CCM

36. Disposition • Patients who remain completely asymptomatic for 6 hours after an oral overdose of normal-release preparations can be safely referred for psychiatric evaluation, with medical consultation for the first 24 hours. Zohair Al Aseri MD,FRCPC EM & CCM

37. CALCIUM CHANNEL BLOCKERS Perspective • Most fatalities occur with verapamil, but severe toxicity and death have been reported for most drugs of this class. Zohair Al Aseri MD,FRCPC EM & CCM

38. Pathophysiology Calcium channel antagonists • block the slow calcium channels in the myocardium and vascular smooth muscle, leading to coronary and peripheral vasodilation. • reduce cardiac contractility • depress SA nodal activity • slow AV conduction. Zohair Al Aseri MD,FRCPC EM & CCM

39. Pathophysiology • Both verapamil and diltiazem act on the heart and blood vessels, whereas nifedipine causes primarily vasodilation. • In the pancreas, calcium channel blockade inhibits insulin release, resulting in hyperglycemia. • As with beta-blockers, selectivity is lost in cases of overdose Zohair Al Aseri MD,FRCPC EM & CCM

40. Pathophysiology • All calcium channel blockers are rapidly absorbed • Onset of action and toxicity ranges from less than 30 minutes to 60 minutes • Peak effect of nifedipine can occur as early as 20 minutes after ingestion, Zohair Al Aseri MD,FRCPC EM & CCM

41. Pathophysiology • Peak effect of sustained-release verapamil can be delayed for many hours. • High protein binding and Vd greater than 1 to 2 L/kg make hemodialysis or hemoperfusion ineffective. • Fortunately (except with sustained-release preparations), their half-lives are relatively short, limiting toxicity to 24 to 36 hours. Zohair Al Aseri MD,FRCPC EM & CCM

42. Selected Characteristics of Some Calcium Channel Blockers Zohair Al Aseri MD,FRCPC EM & CCM

43. MANIFESTATIONS AND COMPLICATIONS OF CALCIUM CHANNEL BLOCKER POISONING Zohair Al Aseri MD,FRCPC EM & CCM

44. Diagnostic Strategies • Serum levels of calcium antagonists are not available • Glucose and Electrolytes (including calcium and magnesium). Hyperglycemia secondary to insulin inhibition occurs occasionally, but mild and short-lived requires no treatment. • Lactic acidosis occurs with hypotension and hypoperfusion. Zohair Al Aseri MD,FRCPC EM & CCM

45. Diagnostic Strategies • ECG • A prolonged QRS or QT interval suggests bepridil or a co-ingested cardiac toxin such as a TCA. Zohair Al Aseri MD,FRCPC EM & CCM

46. Management • IV • O2 • Cardiac monitoring • Vomiting is a powerful vagal stimulus that can exacerbate bradycardia and heart block. • No evidence for activated charcoal Zohair Al Aseri MD,FRCPC EM & CCM

47. Hypotension and Bradycardia • Atropine (0.5–1 mg, up to 3 mg for adults, and 0.02 mg/kg for children, minimum 0.1 mg). • Atropine's effect is short-lived • If symptomatic bradycardia or heart block persists, the next step is a pacemaker or chronotrope such as isoproterenol. Zohair Al Aseri MD,FRCPC EM & CCM

48. Hypotension and BradycardiaIntravenous calcium • have considerable effect on contractility but their effect on bradycardia, AV block, and peripheral vasodilation is often poor. Zohair Al Aseri MD,FRCPC EM & CCM

49. Hypotension and Bradycardia • Epinephrine, norepinephrine, and dobutamine have also led to successful outcomes. Zohair Al Aseri MD,FRCPC EM & CCM

50. Hypotension and Bradycardia • Glucagon has also been used for its inotropic and chronotropic effects. Zohair Al Aseri MD,FRCPC EM & CCM